Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Más filtros

Base de datos
Tipo del documento
Intervalo de año de publicación
1.
Adv Neonatal Care ; 23(5): 401-408, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37018178

RESUMEN

BACKGROUND: Increased noxious noise leads to adverse short-term and long-term effects on the growing neonate. The American Academy of Pediatrics recommends maintaining a noise level of less than 45 decibels (dBA). The average baseline noise level in an open-pod neonatal intensive care unit (NICU) was 62.6 dBA. PURPOSE: The purpose of this pilot project was to reduce the average noise levels by 39% at the end of an 11-week period. METHODS: The location of the project was in a large, high-acuity level IV open-pod layout NICU that consisted of 4 pods, one of which was cardiac-focused. The average baseline noise level in the cardiac pod was 62.6 dBA in a 24-hour period. Noise levels were not monitored before this pilot project. This project was implemented over an 11-week period. Several modes of education were used for parents and staff. Post-education, Quiet Times were implemented at set times twice daily. Noise levels were monitored for 4 weeks during Quiet Times, with weekly noise level updates for staff. General noise levels were collected a final time to evaluate the overall change in the average noise levels. RESULTS: At the end of the project, noise levels decreased from 62.6 dBA to 54 dBA, a 13.7% reduction. IMPLICATIONS FOR PRACTICE AND RESEARCH: At the end of this pilot project it was noted that: Online modules were the best way to educate staff. Parents should be included in the implementation of quality improvement. Healthcare providers need to know and understand that they can make preventative changes to improve the outcomes of the population.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Mejoramiento de la Calidad , Recién Nacido , Humanos , Niño , Proyectos Piloto , Ruido/prevención & control , Personal de Salud
2.
Int J Mol Sci ; 24(8)2023 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-37108119

RESUMEN

Sporadic Alzheimer's disease (sAD) represents a serious and growing worldwide economic and healthcare burden. Almost 95% of current AD patients are associated with sAD as opposed to patients presenting with well-characterized genetic mutations that lead to AD predisposition, i.e., familial AD (fAD). Presently, the use of transgenic (Tg) animals overexpressing human versions of these causative fAD genes represents the dominant research model for AD therapeutic development. As significant differences in etiology exist between sAD and fAD, it is perhaps more appropriate to develop novel, more sAD-reminiscent experimental models that would expedite the discovery of effective therapies for the majority of AD patients. Here we present the oDGal mouse model, a novel model of sAD that displays a range of AD-like pathologies as well as multiple cognitive deficits reminiscent of AD symptomology. Hippocampal cognitive impairment and pathology were delayed with N-acetyl-cysteine (NaC) treatment, which strongly suggests that reactive oxygen species (ROS) are the drivers of downstream pathologies such as elevated amyloid beta and hyperphosphorylated tau. These features demonstrate a desired pathophenotype that distinguishes our model from current transgenic rodent AD models. A preclinical model that presents a phenotype of non-genetic AD-like pathologies and cognitive deficits would benefit the sAD field, particularly when translating therapeutics from the preclinical to the clinical phase.


Asunto(s)
Enfermedad de Alzheimer , Trastornos del Conocimiento , Ratones , Humanos , Animales , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/genética , Memoria , Animales Modificados Genéticamente , Modelos Animales de Enfermedad
3.
BMC Med Educ ; 22(1): 667, 2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36085042

RESUMEN

BACKGROUND: Nephrology is a subject which is challenged by a lack of applicants for trainee places. This study addresses the attitudes of medical students towards the subject and explores the causes of this lack of interest amongst potential specialty trainees. METHODS: Students were asked to complete a survey ranking their attitudes towards nephrology and other specialties. This data was collated and analysed to show trends and allow comparison of the attitudes towards each specialty. RESULTS: Students felt that along with geriatrics, their least favourite subject was nephrology. Students felt unconfident in diagnosing, managing and understanding chronic conditions more so than acute conditions. Nephrology was consistently amongst the least popular subject for all areas of diagnosis, management and pathophysiology. Renal anatomy was the only area of nephrology that students felt confident in. The less popular specialties of nephrology and geriatrics had the greatest room for improvement when directly instructed in specialty medical training. CONCLUSIONS: Nephrology remains a problematic and unpopular specialty for medical students, driving their unwillingness to consider it as a future career route. This study identifies areas of misconception amongst medical students toward the specialty and highlights areas for improvement in renal training for students.


Asunto(s)
Geriatría , Nefrología , Estudiantes de Medicina , Actitud , Selección de Profesión , Humanos , Nefrología/educación , Estudios Retrospectivos
4.
J Appl Microbiol ; 132(5): 3853-3869, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35262250

RESUMEN

AIMS: We evaluated two species of human oral commensal streptococci in protection against dental caries induced by Streptococcus mutans. METHODS AND RESULTS: Candidate probiotics, Streptococcus sp. A12, Streptococcus sanguinis BCC23 and an arginine deiminase mutant of BCC23 (∆arcADS) were tested for their ability to reduce S. mutans-induced caries in an established mouse model. Mice were colonized with a probiotic, challenged with S. mutans, then intermittently reinoculated with a probiotic strain. Oral colonization of each strain and autochthonous bacteria was assessed by quantitative polymerase chain reaction. Both BCC23 strains, but not A12, were associated with markedly reduced sulcal caries, persistently colonized mucosal and dental biofilms, and significantly lowered S. mutans counts. All three strains enhanced mucosal colonization of autochthonous bacteria. In a follow-up experiment, when S. mutans was established first, dental and mucosal colonization of S. mutans was unaltered by a subsequent challenge with either BCC23 strain. Results between BCC23 and BCC23 ∆arcADS were equivalent. CONCLUSIONS: BCC23 is a potential probiotic to treat patients at high caries risk. Its effectiveness is independent of ADS activity, but initial dental cleaning to enhance establishment in dental biofilms may be required. SIGNIFICANCE AND IMPACT OF THE STUDY: In vivo testing of candidate probiotics is highly informative, as effectiveness is not always reflected by genotype or in vitro behaviours.


Asunto(s)
Caries Dental , Probióticos , Animales , Biopelículas , Caries Dental/prevención & control , Humanos , Ratones , Probióticos/farmacología , Streptococcus/genética , Streptococcus mutans/genética , Streptococcus sanguis
5.
Appl Environ Microbiol ; 87(4)2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33277269

RESUMEN

A collection of 113 Streptococcus strains from supragingival dental plaque of caries-free individuals were recently tested in vitro for direct antagonism of the dental caries pathogen Streptococcus mutans, and for their capacity for arginine catabolism via the arginine deiminase system (ADS). To advance their evaluation as potential probiotics, twelve strains of commensal oral streptococci with various antagonistic and ADS potentials were assessed in a mouse model for oral (i.e., oral mucosal pellicles and saliva) and dental colonization under four diets (healthy or high-sucrose, with or without prebiotic arginine). Colonization by autochthonous bacteria was also monitored. One strain failed to colonize, whereas oral colonization by the other eleven strains varied by 3 log units. Dental colonization was high for five strains regardless of diet, six strains increased colonization with at least one high-sucrose diet, and added dietary arginine decreased dental colonization of two strains. Streptococcus sp. A12 (high in vitro ADS activity and antagonism) and two engineered mutants lacking the ADS (ΔarcADS) or pyruvate oxidase-mediated H2O2 production (ΔspxB) were tested for competition against S. mutans UA159. A12 wild type and ΔarcADS colonized only transiently, whereas ΔspxB persisted, but without altering oral or dental colonization by S. mutans In testing four additional candidates, S. sanguinis BCC23 markedly attenuated S. mutans' oral and dental colonization, enhanced colonization of autochthonous bacteria, and decreased severity of smooth surface caries under highly cariogenic conditions. Results demonstrate the utility of the mouse model to evaluate potential probiotics, revealing little correlation between in vitro antagonism and competitiveness against S. mutans in vivo IMPORTANCE Our results demonstrate in vivo testing of potential oral probiotics can be accomplished and can yield information to facilitate the ultimate design and optimization of novel anti-caries probiotics. We show human oral commensals associated with dental health are an important source of potential probiotics that may be used to colonize patients under dietary conditions of highly varying cariogenicity. Assessment of competitiveness against dental caries pathogen Streptococcus mutans and impact on caries identified strains or genetic elements for further study. Results also uncovered strains that enhanced oral and dental colonization by autochthonous bacteria when challenged with S. mutans, suggesting cooperative interactions for future elucidation. Distinguishing a rare strain that effectively compete with S. mutans under conditions that promote caries further validates our systematic approach to more critically evaluate probiotics for use in humans.

6.
Front Microbiol ; 11: 2119, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33013773

RESUMEN

Lack of LrgAB renders cariogenic Streptococcus mutans more sensitive to oxidative stress, as well as limits the capacity of this organism to re-uptake pyruvate upon starvation. This study was aimed at investigating the ecological and metabolic contribution of LrgAB to competitive fitness, using S. mutans strains, that either lack or overexpress lrgAB. These experiments revealed that impaired aerobic growth of the ΔlrgAB mutant can be effectively restored by supplementation of pyruvate, and that perturbated expression of lrgAB significantly affects pyruvate flux and the conversion of pyruvate to acetyl-CoA by the Pdh pathway, verifying that LrgAB is closely linked to pyruvate catabolism. In vitro competition assays revealed that LrgAB plays an important role in S. mutans competition with H2O2-producing S. gordonii, an interaction which can also be modulated by external pyruvate. However, no obvious competitive disadvantage was observed against S. gordonii by either the S. mutans lrgAB mutant or lrgAB overexpression strain in vivo using a mouse caries model. Organic acid analysis of mouse dental biofilms revealed that metabolites produced by the host and/or dental plaque microbiota could complement the deficiency of a lrgAB mutant, and favored S. mutans establishment compared to S. gordonii. Collectively, these results reinforce the importance of the oral microbiota and the metabolic environment in the oral cavity battleground, and highlight that pyruvate uptake through LrgAB may be crucial for interspecies competition that drives niche occupancy.

7.
Mol Metab ; 39: 101009, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32413585

RESUMEN

OBJECTIVE: Recent evidence suggests the substantial pathogenic role of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in the development of low-grade chronic inflammatory response, known as "metaflammation," which contributes to obesity and type 2 diabetes. In this study, we investigated the effects of the JAK1/2 inhibitor baricitinib, recently approved for the treatment of rheumatoid arthritis, in a murine high-fat-high sugar diet model. METHODS: Male C57BL/6 mice were fed with a control normal diet (ND) or a high-fat-high sugar diet (HD) for 22 weeks. A sub-group of HD fed mice was treated with baricitinib (10 mg/kg die, p.o.) for the last 16 weeks (HD + Bar). RESULTS: HD feeding resulted in obesity, insulin-resistance, hypercholesterolemia and alterations in gut microbial composition. The metabolic abnormalities were dramatically reduced by chronic baricitinib administration. Treatment of HD mice with baricitinib did not change the diet-induced alterations in the gut, but restored insulin signaling in the liver and skeletal muscle, resulting in improvements of diet-induced myosteatosis, mesangial expansion and associated proteinuria. The skeletal muscle and renal protection were due to inhibition of the local JAK2-STAT2 pathway by baricitinib. We also demonstrated that restored tissue levels of JAK2-STAT2 activity were associated with a significant reduction in cytokine levels in the blood. CONCLUSIONS: In summary, our data suggest that the JAK2-STAT2 pathway may represent a novel candidate for the treatment of diet-related metabolic derangements, with the potential for EMA- and FDA-approved JAK inhibitors to be repurposed for the treatment of type 2 diabetes and/or its complications.


Asunto(s)
Azetidinas/farmacología , Dieta Alta en Grasa/efectos adversos , Inhibidores de las Cinasas Janus/farmacología , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/metabolismo , Purinas/farmacología , Pirazoles/farmacología , Sulfonamidas/farmacología , Animales , Antiinflamatorios/farmacología , Biomarcadores , Modelos Animales de Enfermedad , Metabolismo Energético/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Glucosa/metabolismo , Inmunohistoquímica , Inflamación/tratamiento farmacológico , Inflamación/etiología , Inflamación/metabolismo , Insulina/metabolismo , Janus Quinasa 2/metabolismo , Masculino , Enfermedades Metabólicas/diagnóstico , Enfermedades Metabólicas/tratamiento farmacológico , Ratones , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Factores de Transcripción STAT/metabolismo , Transducción de Señal/efectos de los fármacos
8.
JAMIA Open ; 3(4): 619-627, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33758798

RESUMEN

OBJECTIVES: Patient-generated health data (PGHD) are clinically relevant data captured by patients outside of the traditional care setting. Clinical use of PGHD has emerged as an essential issue. This study explored the evidence to determine the extent of and describe the characteristics of PGHD integration into electronic health records (EHRs). METHODS: In August 2019, we conducted a systematic scoping review. We included studies with complete, partial, or in-progress PGHD and EHR integration within a clinical setting. The retrieved articles were screened for eligibility by 2 researchers, and data from eligible articles were abstracted, coded, and analyzed. RESULTS: A total of 19 studies met inclusion criteria after screening 9463 abstracts. Most of the study designs were pilots and all were published between 2013 and 2019. Types of PGHD were biometric and patient activity (57.9%), questionnaires and surveys (36.8%), and health history (5.3%). Diabetes was the most common patient condition (42.1%) for PGHD collection. Active integration (57.9%) was slightly more common than passive integration (31.6%). We categorized emergent themes into the 3 steps of PGHD flow. Themes emerged concerning resource requirements, data delivery to the EHR, and preferences for review. DISCUSSION: PGHD integration into EHRs appears to be at an early stage. PGHD have the potential to close health care gaps and support personalized medicine. Efforts are needed to understand how to optimize PGHD integration into EHRs considering resources, standards for EHR delivery, and clinical workflows.

9.
J Pain Symptom Manage ; 59(3): 609-617, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31711970

RESUMEN

CONTEXT: A key challenge in nursing homes (NHs) is how to attain and clarify resident preferences for care and then communicate these preferences to family members and staff. OBJECTIVES: We evaluated the feasibility and acceptability of Me & My Wishes-person-centered videos of residents discussing their preferences for daily and end-of-life (EOL) care. METHODS: For this descriptive study, Me & My Wishes videos were created with residents in three NHs in the Pacific Northwest. Feasibility was evaluated by tracking resident enrollment, completing and sharing their video, and conducting debriefing interviews to ascertain residents' impressions of the recording process and personalized conversation. After viewing the video, staff and family assessed communication quality via survey-the extent to which they perceived messages from the video (e.g., preferences for EOL) to be timely, accurate, adequate, complete, and credible and items on resident preferences for daily and EOL care. RESULTS: Twenty of 33 residents approached created videos; 18 of these residents shared their videos with family or staff. Residents reported that they liked the opportunity to express their wishes. On a scale of 1-7 (lower is better), mean ratings were 2.0 (family) and 1.3 (staff) for communicating preferences for daily care; 1.9 (family) and 1.2 (staff) for communicating preferences for EOL. Both family and staff reported increased knowledge about resident preferences for daily and EOL care. CONCLUSION: This research supports the feasibility and acceptability of a videotaping approach (Me & My Wishes) for viewing, listening, and discussing residents' preferences for daily and EOL care.


Asunto(s)
Casas de Salud , Prioridad del Paciente , Cuidado Terminal , Grabación en Video , Comunicación , Humanos , Encuestas y Cuestionarios
10.
BMJ Open ; 9(12): e033073, 2019 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-31852707

RESUMEN

INTRODUCTION: The objective of this study is to determine the extent and describe the nature of patient-generated health data (PGHD) integration into electronic health records (EHRs) using systematic scoping methods to review the available literature. PGHD have the potential to enhance decision making by providing the valuable information that may not be ordinarily captured during a routine care visit. These data which are captured from mobile devices, such as smartphones, activity trackers and other sensors, should be integrated into clinical workflows to allow for optimal use by clinicians. METHODS AND ANALYSIS: This study aims to conduct a rigorous scoping review to explore evidence related to the integration of PGHD into EHRs. Using the framework developed by Arksey and O'Malley, we will create a systematic search strategy, chart data from the relevant articles, and use a qualitative, thematic approach to analyse the data. This review will enable the identification of types of integration and describe challenges and barriers to integrating PGHD. ETHICS AND DISSEMINATION: Database searches will be initiated in June 2019. The review is expected to be completed by October 2019. As the content of the full-text articles emerges, the authors will summarise the characteristics related to the integration of PGHD. The findings of this scoping review will identify research gaps and present implications for future research.


Asunto(s)
Registros Electrónicos de Salud/normas , Informática Médica/métodos , Datos de Salud Generados por el Paciente/métodos , Integración de Sistemas , Humanos , Proyectos de Investigación , Literatura de Revisión como Asunto
11.
Semin Oncol Nurs ; 34(1): 60-71, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29306523

RESUMEN

OBJECTIVE: To identify the unique needs of lesbian, gay, bisexual, and transgender (LGBT) cancer patients and caregivers, and review recommendations supporting more effective and inclusive palliative and end-of-life care. DATA SOURCES: Published research and clinical guidelines. CONCLUSION: Transitions in care raise particular challenges for LGBT patients, including provider communication, perceptions of safety and acceptance, and assessing and respecting patients' definitions of family and spirituality. IMPLICATIONS FOR NURSING PRACTICE: LGBT patients and their caregivers need competent nurses to support them, especially during transitions. Implementing LGBT-inclusive education, training, and practice will improve outcomes for LGBT cancer patients and their caregivers - and potentially all patients.


Asunto(s)
Cuidadores/psicología , Familia/psicología , Neoplasias/terapia , Cuidados Paliativos/organización & administración , Minorías Sexuales y de Género , Cuidado Terminal/organización & administración , Continuidad de la Atención al Paciente , Revelación , Femenino , Cuidados Paliativos al Final de la Vida/organización & administración , Humanos , Masculino , Neoplasias/enfermería , Relaciones Enfermero-Paciente , Apoyo Social , Espiritualidad , Estados Unidos
12.
J Oral Maxillofac Surg ; 73(3): 541-9, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25683044

RESUMEN

PURPOSE: The purpose of this study was to address the following clinical question: Is immediate reconstruction of the mandible with a nonvascularized bone graft after resection of benign pathology a viable treatment option? Another purpose was to determine whether any variables affect the success of this treatment approach. MATERIALS AND METHODS: The authors implemented a retrospective cohort study from a sample of patients diagnosed with a benign tumor of the mandible who were treated with segmental resection and primary reconstruction with an autogenous nonvascularized bone graft. The predictor variables were age, gender, lesion size, and diagnosis, and the outcome variable was graft success determined by re-establishment of mandibular continuity with sufficient bone for implant placement. The χ(2) test was used for statistical analysis of the categorical data and P values less than .05 were considered statistically significant. RESULTS: Twenty patients with benign mandibular tumors were treated with transoral resection and immediate reconstruction with nonvascularized bone grafts. The mean age was 28.3 years (range, 9 to 63 yr) and 55% (11 of 20) were men. The most common lesion type was ameloblastoma (13 of 20) and all patients underwent reconstruction with autogenous anterior iliac crest bone grafting. Ninety percent of patients (18 of 20) had successful reconstruction. Ten patients underwent successful implant placement and restoration. CONCLUSIONS: Using careful patient selection, treatment of benign pathology with transoral resection and immediate reconstruction with a nonvascularized bone graft from the anterior iliac crest can be successful. In addition, the total treatment time from implant restoration to return to preoperative function is minimized. Therefore, this method of treatment is a viable treatment option and an alternative to delayed reconstruction or reconstruction with vascularized bone flaps.


Asunto(s)
Autoinjertos/trasplante , Trasplante Óseo/métodos , Neoplasias Mandibulares/cirugía , Reconstrucción Mandibular/métodos , Adolescente , Adulto , Ameloblastoma/cirugía , Placas Óseas , Niño , Estudios de Cohortes , Diseño Asistido por Computadora , Implantación Dental Endoósea/métodos , Remoción de Dispositivos , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Reconstrucción Mandibular/instrumentación , Persona de Mediana Edad , Modelos Anatómicos , Planificación de Atención al Paciente , Reoperación , Estudios Retrospectivos , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/cirugía , Resultado del Tratamiento , Adulto Joven
13.
Nat Med ; 19(7): 901-908, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23793099

RESUMEN

Here we show that glioblastoma express high levels of branched-chain amino acid transaminase 1 (BCAT1), the enzyme that initiates the catabolism of branched-chain amino acids (BCAAs). Expression of BCAT1 was exclusive to tumors carrying wild-type isocitrate dehydrogenase 1 (IDH1) and IDH2 genes and was highly correlated with methylation patterns in the BCAT1 promoter region. BCAT1 expression was dependent on the concentration of α-ketoglutarate substrate in glioma cell lines and could be suppressed by ectopic overexpression of mutant IDH1 in immortalized human astrocytes, providing a link between IDH1 function and BCAT1 expression. Suppression of BCAT1 in glioma cell lines blocked the excretion of glutamate and led to reduced proliferation and invasiveness in vitro, as well as significant decreases in tumor growth in a glioblastoma xenograft model. These findings suggest a central role for BCAT1 in glioma pathogenesis, making BCAT1 and BCAA metabolism attractive targets for the development of targeted therapeutic approaches to treat patients with glioblastoma.


Asunto(s)
Aminoácidos de Cadena Ramificada/metabolismo , Neoplasias Encefálicas/metabolismo , Proliferación Celular , Glioma/metabolismo , Transaminasas/fisiología , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Femenino , Glioma/genética , Glioma/patología , Células HEK293 , Humanos , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/fisiología , Metabolismo/genética , Ratones , Ratones Desnudos , Modelos Biológicos , Transaminasas/genética , Transaminasas/metabolismo
14.
Bioconjug Chem ; 23(4): 688-97, 2012 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-22369515

RESUMEN

Urea-based inhibitors of the prostate-specific membrane antigen (PSMA) represent low-molecular-weight pepidomimetics showing the ability to image PSMA-expressing prostate tumors. The highly efficient, acyclic Ga(III) chelator N,N'-bis [2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N'- diacetic acid (HBED-CC) was introduced as a lipophilic side chain into the hydrophilic pharmacophore Glu-NH-CO-NH-Lys which was found favorable to interact with the PSMA "active binding site". This report describes the syntheses, in vitro binding analyses, and biodistribution data of the radiogallium labeled PSMA inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC in comparison to the corresponding DOTA conjugate. The binding properties were analyzed using competitive cell binding and enzyme-based assays followed by internalization experiments. Compared to the DOTA-conjugate, the HBED-CC derivative showed reduced unspecific binding and considerable higher specific internalization in LNCaP cells. The (68)Ga complex of the HBED-CC ligand exhibited higher specificity for PSMA expressing tumor cells resulting in improved in vivo properties. (68)Ga labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC showed fast blood and organ clearances, low liver accumulation, and high specific uptake in PSMA expressing organs and tumor. It could be demonstrated that the PET-imaging property of a urea-based PSMA inhibitor could significantly be improved with HBED-CC.


Asunto(s)
Antígenos de Superficie/metabolismo , Glutamato Carboxipeptidasa II/antagonistas & inhibidores , Glutamato Carboxipeptidasa II/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Tomografía de Emisión de Positrones/métodos , Inhibidores de Proteasas/química , Urea/química , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica , Quelantes/química , Ácido Edético/análogos & derivados , Ácido Edético/química , Radioisótopos de Galio , Humanos , Marcaje Isotópico , Masculino , Ratones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Inhibidores de Proteasas/metabolismo , Inhibidores de Proteasas/farmacocinética , Estereoisomerismo
15.
Phytochemistry ; 77: 226-37, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22277734

RESUMEN

Longan (Dimocarpus longan Lour, syn. Euphoria longan Lam.) represents an important fruit in Northern Thailand and has significant economic impact. The fruit is either consumed fresh or as commercially prepared dried and canned products. The canning industry in Thailand produces considerable quantities of waste products, in particular Longan seeds. Because these seeds may be an exploitable source of natural phenolic antioxidants, it was of interest to identify, purify and quantitate the major potential antioxidant phenolics contained therein. The polyphenolic fraction from ground Longan seeds was obtained by extraction with methanol after delipidation with hexane. The hexane extract contained predominantly long-chain fatty acids with major contributions from palmitic (35%) and oleic (28%) acids. The polyphenolic fraction (80.90 g/kg dry weight) was dominated by ellagic acid (25.84 g/kg) and the known ellagitannins corilagin (13.31 g/kg), chebulagic acid (13.06 g/kg), ellagic acid 4-O-α-l-arabinofuranoside (9.93 g/kg), isomallotinic acid (8.56 g/kg) and geraniin (5.79 g/kg). Structure elucidation was performed with mass spectrometry and complete assignment of (1)H and (13)C NMR signals. The methanol extracts exhibited strong antioxidant capacities with an IC(50) of 154 µg/ml for reactive oxygen species attack on salicylic acid and 78 µg/ml for inhibition of xanthine oxidase in the hypoxanthine/xanthine oxidase assay. The extracts were less effective in the 2-deoxyguanosine assay (IC(50)=2.46 mg/ml), indicating that gallates along with ellagic acid and its congeners exert their potential antioxidant effects predominantly by precipitation of proteins such as xanthine oxidase. This was confirmed for the pure compounds gallic acid, methyl gallate, ellagic acid and corilagin.


Asunto(s)
Antioxidantes/química , Taninos Hidrolizables/química , Sapindaceae/química , Semillas/química , Antioxidantes/aislamiento & purificación , Antioxidantes/metabolismo , Cromatografía Líquida de Alta Presión , Recuperación de Fluorescencia tras Fotoblanqueo , Taninos Hidrolizables/aislamiento & purificación , Taninos Hidrolizables/metabolismo , Hipoxantina/química , Metabolismo de los Lípidos , Espectrometría de Masas , Resonancia Magnética Nuclear Biomolecular , Fenoles/química , Fenoles/aislamiento & purificación , Especies Reactivas de Oxígeno/química , Ácido Salicílico/química , Sapindaceae/metabolismo , Semillas/metabolismo , Tailandia , Xantina Oxidasa/química
16.
Chem Res Toxicol ; 25(1): 162-9, 2012 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-22148471

RESUMEN

Methylation of cytidine at dCpdG sequences regulates gene expression and is altered in many chronic inflammatory diseases. Inflammation generates lipid peroxidation (LPO) products which can react with deoxycytidine, deoxyadenosine, and deoxyguanosine in DNA to form pro-mutagenic exocyclic etheno-nucleoside residues. Since 5-methyl-2'-deoxycytidine (5mdC) residues exhibit increased nucleophilicity at N3, they should be even better targets for LPO products. We synthesized and characterized 3,N(4)-etheno-5-methyl-2'-deoxycytidine-3'-phosphate and showed that LPO products can indeed form the corresponding etheno-5mdC (ε5mdC) lesion in DNA in vitro. Our newly developed (32)P-postlabeling method was subsequently used to detect ε5mdC lesions in DNA from human white blood cells, lung, and liver at concentrations 4-10 times higher than that observed for etheno adducts on nonmethylated cytidine. Our new detection method can now be used to explore the hypothesis that this DNA lesion perturbs the DNA methylation status.


Asunto(s)
Aductos de ADN , ADN/metabolismo , Desoxicitidina/análogos & derivados , Acetaldehído/análogos & derivados , Acetaldehído/metabolismo , Ácido Araquidónico/metabolismo , Metilación de ADN , Desoxicitidina/metabolismo , Femenino , Genoma , Humanos , Leucocitos/metabolismo , Peroxidación de Lípido , Hígado/metabolismo , Pulmón/metabolismo
17.
Glycobiology ; 21(4): 493-502, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21106561

RESUMEN

The EUROCarbDB project is a design study for a technical framework, which provides sophisticated, freely accessible, open-source informatics tools and databases to support glycobiology and glycomic research. EUROCarbDB is a relational database containing glycan structures, their biological context and, when available, primary and interpreted analytical data from high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance experiments. Database content can be accessed via a web-based user interface. The database is complemented by a suite of glycoinformatics tools, specifically designed to assist the elucidation and submission of glycan structure and experimental data when used in conjunction with contemporary carbohydrate research workflows. All software tools and source code are licensed under the terms of the Lesser General Public License, and publicly contributed structures and data are freely accessible. The public test version of the web interface to the EUROCarbDB can be found at http://www.ebi.ac.uk/eurocarb.


Asunto(s)
Carbohidratos/química , Bases de Datos como Asunto , Programas Informáticos , Animales , Conformación de Carbohidratos , Biología Computacional , Glicómica , Humanos , Modelos Moleculares , Peso Molecular , Sistemas en Línea
19.
Phytochemistry ; 71(10): 1132-48, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20451939

RESUMEN

Thirty-four polyphenolic substances in methanol extracts of the fruits of Terminalia bellerica, Terminalia chebula and Terminalia horrida, three plants used in Egyptian folk medicine, were initially identified by HPLC-ESI-MS and quantitated by analytical HPLC after column chromatography on Sephadex LH-20. After purification by semi-preparative HPLC the compounds were identified by their mass and fragmentation patterns using ESI-MS-MS. For several compounds detailed 1H/13C NMR analysis at 600 MHz was performed. Two polyphenolics, namely 4-O-(4''-O-galloyl-alpha-L-rhamnopyranosyl)ellagic acid and 4-O-(3'',4''-di-O-galloyl-alpha-L-rhamnopyranosyl)ellagic acid were identified by NMR. Antioxidant capacities of the raw fruit extracts and the major isolated substances were determined using the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), oxygen radical absorbance capacity (ORAC) and ferric reducing ability of plasma (FRAP) in vitro assays and indicated that chebulic ellagitannins have high activity which may correlate with high potential as cancer chemopreventive agents. Therefore, further studies (metabolism, bioavailability and toxicity) of the polyphenolics in Terminalia species using preclinical models and in vivo human intervention trials are warranted.


Asunto(s)
Antioxidantes/análisis , Flavonoides/análisis , Fenoles/análisis , Plantas Medicinales/química , Terminalia/química , Antioxidantes/química , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión , Flavonoides/química , Flavonoides/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Fenoles/química , Fenoles/farmacología , Polifenoles , Especificidad de la Especie , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem
20.
J Matern Fetal Neonatal Med ; 21(9): 652-9, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18828058

RESUMEN

OBJECTIVE: The fetus is thought to play a central role in the onset of labor. Pulmonary surfactant protein (SP)-A, secreted by the maturing fetal lung, has been implicated in the mechanisms initiating parturition in mice. The present study was conducted to determine whether amniotic fluid concentrations of SP-A and SP-B change during human parturition. STUDY DESIGN: Amniotic fluid SP-A and SP-B concentrations were measured with a sensitive and specific ELISA in the following groups of pregnant women: (1) mid-trimester of pregnancy, between 15 and 18 weeks of gestation (n = 29), (2) term pregnancy not in labor (n = 28), and (3) term pregnancy in spontaneous labor (n = 26). Non-parametric statistics were used for analysis. RESULTS: SP-A was detected in all amniotic fluid samples. SP-B was detected in 24.1% (7/29) of mid-trimester samples and in all samples at term. The median amniotic fluid concentrations of SP-A and SP-B were significantly higher in women at term than in women in the mid-trimester (SP-A term no labor: median 5.6 microg/mL, range 2.2-15.2 microg/mL vs. mid-trimester: median 1.64 microg/mL, range 0.1-4.7 microg/mL, and SP-B term no labor: median 0.54 microg/mL, range 0.17-1.99 microg/mL vs. mid-trimester: median 0 microg/mL, range 0-0.35 microg/mL; both p < 0.001). The median amniotic fluid SP-A concentration in women at term in labor was significantly lower than that in women at term not in labor (term in labor: median 2.7 microg/mL, range 1.2-10.1 microg/mL vs. term no labor: median 5.6 microg/mL, range 2.2-15.2 microg/mL; p < 0.001). There was no significant difference in the median amniotic fluid SP-B concentrations between women in labor and those not in labor (term in labor: median 0.47 microg/mL, range 0.04-1.32 microg/mL vs. term no labor: median 0.54 microg/mL, range 0.17-1.99 microg/mL; p = 0.2). CONCLUSION: The amniotic fluid concentration of SP-A decreases in spontaneous human parturition at term.


Asunto(s)
Líquido Amniótico/metabolismo , Embarazo/metabolismo , Proteína A Asociada a Surfactante Pulmonar/metabolismo , Proteína B Asociada a Surfactante Pulmonar/metabolismo , Nacimiento a Término/metabolismo , Adulto , Estudios Transversales , Femenino , Humanos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA